Acute Respiratory Distress Syndrome (ARDS) is defined as “an acute, diffuse, inflammatory lung injury, leading to increased vascular permeability, increased lung weight and loss of aerated lung tissue.” There is subsequent hypoxia with bilateral radiographic opacities,increased physiological deadspace and reduced lung compliance.
The previous description and definition of ARDS had led to some variation in diagnosis, with subsequent impact of prevalence. The Berlin definition (2011) was therefore composed in response to this, as a joint work by the ESICM, American Thoracic Society, and the Society of Critical Care Medicine. The requirements are:
Acute - within 7 days of a known insult
Bilateral opacities - consistent with pulmonary oedema
Hypoxia - PF ratio < 300 mmHg (40 kPa) on 5 cmH20 PEEP
Not explained by cardiac failure/fluid overload - an objective assessment e.g. echo should be performed in most cases
The severity of ARDS is defined by the degree of hypoxia in the form of the PF ratio (pO2/FiO2).
Mild - 200-300 mmHg (26.6-39.9 kPa)
Moderate - 100-200 mmHg (13.3-26.6 kPa)
Severe - <100 mmHg (<13.3 kPa)
There are a number of causes of ARDS. They are classically split into direct and indirect, although there is some clear overlap. Direct:
Aspiration of gastric contents
The pathophysiology of ARDS has a classic pattern:
Exudative phase (acute)
After the injury to the lungs, there is the exudative phase. This step has several components to it:
Alveolocapillary disruption leading to pulmonary oedema
The injury leads to disruption of the alveolocapillary barrier, leading to movement of proteins and fluid into the alveoli and interstitium, with opposite movement of cytokines and surfactant into the capillaries. There is also migration of neutrophils into the alveoli, with activation and release of injuries (reactive oxygen species, protease) and inflammatory (cytokines) substances. Dysfunction of the haemostatic mechanisms leads to the formation of microthrombi in the pulmonary vasculature. The changes are not uniform throughout the lung, but actually in a fairly patchy manner. There is a preponderance to dependent areas of lung.
The pathophysiology has led to the term ‘baby lung’. This refers to the fact that there can be a high proportion of lung with is not free for ventilation due to the ARDS pathophysiological changes. This leads to only a small volume of lung that will effectively participate in gas exchange, and more importantly, which will be effectively ventilated. This smaller volume makes this part of the lung more vulnerable to excessive volumes and pressures that may lead to injury.
Additional changes to lung mechanics and function that arise from this include:
Increased V/Q mismatch - shunting and deadspace
Pulmonary vasoconstriction and hypertension
Hypoxia is an important consequence of these changes, and can be severe.
There are some key features of mechanical ventilation which can contribute to the inflammatory process of ARDS:
Atelectrauma - repeated opening and closing of alveoli.
These processes can propagate the inflammatory process, leading to a vicious circle.
Resolution of the ARDS will usually occur with appropriate treatment, including removal of the triggering stimuli. Propagation of type 2 pneumocyte cells within the alveoli occuring which can help clearance of the alveoli, before transforming into type 1 cells.
ARDS is primarily a clinical diagnosis. A few investigations will aid in the assessment of alternative or related causes e.g. respiratory pathology
CT can be useful to provide additional detail on lung pathology, but transfer to CT scan is not without risk. Echo can assess cardiac function to assess for any contribution. Lung US may provide a novel method of assessment.
There is (currently) no specific treatment for ARDS, and so management focuses around to minimisation of harm. This can be considered as:
Treating the trigger
Minimising exacerbating lung injury
Avoiding other complications
Treating the Trigger Treating the trigger is an important part of removing the initiating inflammatory stimulus. This will clear vary depending on the cause and in some cases only supportive treatment may be possible.
Minimising Lung Injury Much of the care focuses around the minimisation of further lung injury. The severity of the gas exchange derangement means that a large proportion of patients with ARDS require IMV. This can worsen the condition through the effects of pressure and volume related injury as described above. There are several evidence based components to this:
Low volume ventilation
PP < 30 cmH20
Muscle relaxants - severe ARDS
Fluid balance - unclear
Low Volume Ventilation Given the injury that arises from barotrauma and volutrauma, a low volume ventilation strategy has been shown to improve outcomes. The ARDSnet ARMA study is the classic paper that demonstrated this, comparing 6ml/kg against the ‘traditional’ 12ml/kg. This showed improved survival (31% vs 39.8%) as well as ventilator free days. Alongside this, keeping plateau pressures below 30 cmH2O is also employed to minimise barotrauma. As a consequence of the reduced efficacy of gas exchange that this can lead to, especially in diseased lungs, there is some relaxation of the respiratory gas targets. A target of SpO2 >90% is generally deemed acceptable. Similarly, hypercapnia is tolerated if there isn’t a strong reason to control it (e.g. raised ICP) and any resulting acidosis is not severe or causing problems. The mode of ventilation is not thought to make a strong difference, but a pressure control mode is generally employed to give a clearer idea of plateau pressure. It does not seem that a pressure support mode has a benefit if the volumes and pressures remain the same, as it is these factors which lead to the trauma.
PEEP The theory behind PEEP is to maintain alveolar recruitment and avoid the altelectotrauma of repeated opening and closing. There is no clearly defined PEEP that is beneficial, and an elevation of PEEP clearly also requires an elevation in general airway pressure to maintain a gradient for gas flow. The ARDSnet trial advocated a PEEP ladder that is increased with the FiO2. It may be that the use of PEEP to optimise the lung compliance is important, as increasing overall pressure with a detrimental effect the driving pressure would seem to be deleterious. The form that the ARDS takes may also be important here - more diffuse ARDS is more likely to benefit from improved recruitment with a higher PEEP, whilst more focal disease may have more overdistension.
Prone Ventilation Prone ventilation has been shown to improve the outcomes of patients with severe ARDS. The concept is to improve the ventilation and V/Q status of the dependent lung that is most affected in ARDS. By positioning a patient prone, this lung is now superior, and can benefit from the improved mechanics, with better alveolar recruitment and improved V/Q matching. The PROSEVA trial demonstrated an NNT of 6. The intervention involves 16 hours of prone positioning and is not without risk (loss of lines, pressure injury).
Minimising additional features that are contributing negatively to chest wall compliance are also an important consideration. This may include the positioning in the bed, and ensuring appropriate gastric decompression.
The use of muscle relaxants may also have a role here by reducing any negative effect on chest wall compliance from muscular activity. A 2010 study by Papazian suggested an improved outcome in those with severe disease who received a cisatracurium infusion. The adverse effects of muscle relaxation need careful consideration however.
Fluid management has some relationship to lung status too. Given the disruption of the alveolar-capillary integrity, excessive fluid would theoretically appear to have a negative impact on ARDS. Similarly, improving the capillary oncotic pressure of patients with low albumin (e.g. through albumin administration) would appear to have a decent theoretical basis. There is not a strong evidence base for this currently, but a trend towards more restrictive fluid management strategies appears to be ongoing.
Avoiding Complications These patients are at high risk of many of the other adverse effects of critical illness and so careful attention needs to be paid to ensuring these are minimised. Key areas include:
Stress ulcer prophylaxis
Several other therapies have been trialled in the past to improve outcomes in ARDS but which have no clear benefit or risks of harm:
High frequency oscillation ventilation
Despite the theoretical benefit of high frequency oscillatory ventilation in reducing the pressures and volumes transmitted to the lungs, the research does not support its use. The OSCILLATE trial showed an increased mortality and the OSCAR trial demonstrated no benefit.
ECMO The use of ECMO in severe disease is not fully established or understood. It is discussed in more detail as a therapy elsewhere. It may be a rescue option for patients that are suitable candidates with severe disease in whom it is becoming impossible to oxygenate.
Epidemiology & Outcome
The diagnostic challenges of ARDS have made it hard to establish a clear incidence. There are descriptions of it being over and underdiagnosed, and there is no gold standard against which to compare.
The mortality of ARDS is related to its severity:
Mild - 27%
Moderate - 32%
Severe - 45%
The morbidity of ARDS is increasingly being recognised. Even in patients without a progressive fibrotic disease pathway, cardiorespiratory function remains impaired months and even years after recovery. The condition is also associated with psychological morbidity after ICU and some degree of cognitive impairment.